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Abstract

Introduction: Diabetes is associated with a higher incidence of myocardial infarction (MI). Bone marrow-derived endothelial progenitor cell (EPCs) therapy has been shown to attenuate left ventricular (LV) dysfunction after diabetic MI. Recently the therapeutic performance of stem cells is reported to be largely mediated via exosomes (Exo). However, the autologous transplantation of EPCs in patients with diabetes, which is a common background disease in patients with ischemic heart diseases, yielded modest results, suggesting the compromised cell functions.

Hypothesis: Therefore, we hypothesized that, impaired functional benefits of diabetic EPCs are due to altered exosomal contents and whether modulation of identified targets like specific microRNAs in exosomal cargo can rescue and/or enhance their reparative properties.

Methods: To evaluate this, we isolated Exo from db+ and db/db EPCs and compared their functions in terms of cell survival and angiogenic capacity in vitro. Further, we injected both db+ and db/db EPC exosomes in db+ mouse models of MI and compared their repair ability in vivo.